1-68476965-A-C

Position:

• chr1-68476965-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001114120.3(DEPDC1):​c.2403T>G​(p.Ile801Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DEPDC1 NM_001114120.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.124

Genes affected

DEPDC1 (HGNC:22949): (DEP domain containing 1) Predicted to enable GTPase activator activity. Involved in negative regulation of transcription, DNA-templated. Located in nucleus. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03913176).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEPDC1	NM_001114120.3	c.2403T>G	p.Ile801Met	missense_variant	12/12	ENST00000456315.7	NP_001107592.1
DEPDC1	NM_017779.6	c.1551T>G	p.Ile517Met	missense_variant	11/11		NP_060249.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEPDC1	ENST00000456315.7	c.2403T>G	p.Ile801Met	missense_variant	12/12	1	NM_001114120.3	ENSP00000412292.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2022

The c.2403T>G (p.I801M) alteration is located in exon 12 (coding exon 12) of the DEPDC1 gene. This alteration results from a T to G substitution at nucleotide position 2403, causing the isoleucine (I) at amino acid position 801 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.62
DEOGEN2	Benign	0.0060	T;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.039	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.76	N;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.62	N;N
REVEL	Benign	0.015
Sift	Benign	0.42	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.019	B;B
Vest4		0.055
MutPred		0.33		Gain of disorder (P = 0.0173);.;
MVP		0.11
MPC		0.13
ClinPred		0.044	T
GERP RS		-0.045
Varity_R		0.033
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-68942648;